CRABP-II is a highly sensitive and specific diagnostic molecular marker for pancreatic ductal adenocarcinoma in distinguishing from benign pancreatic conditions

Hum Pathol. 2014 Jun;45(6):1177-83. doi: 10.1016/j.humpath.2014.01.014. Epub 2014 Jan 31.

Abstract

CRABP-II, a retinoic acid binding protein, shuffles retinoic acid from cytoplasm into nucleus and forms a complex with nuclear retinoic acid receptor to facilitate transcriptional activities of retinoic acid. In this study, we studied the expression patterns of CRABP-II in pancreatic ductal adenocarcinoma (PDAC) compared with those in normal pancreas, chronic pancreatitis, and precancerous lesions. We showed no detectable expressions of CRABP-II in normal pancreatic parenchyma, normal ductal epithelium, and chronic pancreatitis. In contrast, the expression of CRABP-II was readily detected in all PDACs including metastatic PDACs. CRABP-II staining was also observed and progressively increased from pancreatic intraepithelial neoplasia 1 to 3. In addition, when fine needle aspiration specimens were evaluated from patients with PDAC, CRABP-II was positive in 55.6% cases if cytology diagnosis was "atypia," and in 87.5% cases, if "malignancy." Our study suggests that CRABP-II is highly and specifically expressed in PDAC and is more commonly expressed in high-grade precursor cancerous lesions than in low-grade lesions. Therefore, overexpression of CRABP-II is a late event of pancreatic carcinogenesis, and it could be used as a diagnostic marker to distinguish PDAC from other benign pancreatic conditions in both resection and cytology specimens.

Keywords: CRABP-II; Cytology; Immunohistochemistry; Pancreatic duct adenocarcinoma; Pancreatic intraepithelial neoplasm; Pathology; Retinoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Pancreatic Diseases / diagnosis*
  • Pancreatic Neoplasms / diagnosis*
  • Receptors, Retinoic Acid / analysis*
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Receptors, Retinoic Acid
  • retinoic acid binding protein II, cellular